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Introducao O uso do anticorpo monoclonal humanizado anti-C5 Eculizumab tem se mostrado extremamente eficaz para controlar a hemolise intravascular cronica na Hemoglobinuria Paroxistica Noturna (HPN). Entretanto, o alto custo desta medicacao e demora na liberacao quando judicializado tem sido impeditivo ao uso em todos os pacientes, especialmente em casos de risco de obito imediato. O Eculizumabe e um medicamento estavel em temperatura ambiente. O frasco manipulado em area limpa classe ISO7, em cabine de seguranca biologica ISO5, e com uso de sistema fechado sem agulha permite a reutilizacao posterior do conteudo que sobra nos frascos (overfill). Com os cuidados tecnicos adequados o volume que sobra e de 1,2 mL por frasco de Eculizumab, que pode ser utilizado em ate 7 dias. Objetivos 1) descrever os custos com pacientes em uso de Eculizumab em um servico de referencia e avaliar a possivel economia com o uso de sobras (overfill) dos frascos pela farmacia hospitalar neste periodo; 2) descrever o beneficio obtido pelos pacientes atendidos. Material e metodos Inclusao: Pacientes com HPN Classica que receberam Eculizumab entre janeiro/2018 e junho/2021, quando a dispensacao se tornou obrigatoria dentro de dependencias hospitalares. Exclusao: recebimento na cidade de origem, antes de 2018 e pacientes com SHU atipica. Foram avaliados o tempo de uso, numero de frascos utilizados e numero de frascos de sobra economizados no periodo de 42 meses, e seu custo. Avaliado custo-oportunidade do uso de frascos de sobras menos o custo final caso nao houvesse essa economia. Resultados 10 pacientes com HPN hemolitica classica em uso de Eculizumab utilizaram o total de 1497 frascos = Custo total (sem contabilizar sobras) = R$ 19.442.505,00. Em 42 meses a manipulacao na area limpa gerou 50 frascos de overfilldo medicamento, sendo o Custo Economizado com sobras = R$ 649.382,29. Utilizacao dos frascos de sobraou overfill Dos 10 pacientes sete utilizaram frascos de sobra em algum momento: seis pacientes utilizaram 22 frascos, sendo 3, 4, 4, 2, 1 e 8 respectivamente, e apenas um paciente utilizou 25 frascos entre julho de 2020 e maio de 2021. Este paciente apresentou Sindrome de Budd-Chiari apos trombose aguda, com alto risco de perda do figado e obito, tromboses sequenciais nao controladas com anticoagulacao padrao, e indicacao de transplante hepatico. Com o uso de frascos de overfill de Eculizumab ainda na internacao o paciente evoluiu com diminuicao da hemolise exacerbada e regressao das tromboses, tendo saido do risco de morte imediata. Alem disso, ficou em uso de sobras por mais 8 meses, ate que a medicacao fosse liberada por via judicial. Um paciente com microangiopatia pos TMO utilizou 3 frascos. Discussao O esforco em evitar gastos desnecessarios e maximizar beneficios dentro dos recursos possiveis tem sido extremamente importante na Economia em Saude. Dentro de um hospital publico que conta com recursos escassos, a perspectiva das pessoas que estao diretamente envolvidas com situacoes catastroficas como a HPN hemolitica/trombogenica pode ser o diferencial entre vida e morte. Neste trabalho foi realizada uma analise de custo oportunidade sob a perspectiva dos pacientes beneficiados e da equipe diretamente envolvida (medicos, farmaceuticos). Observamos uma economia global de R$ 649.382,29 em 42 meses. Com este montante economizado foi possivel cobrir faltas ou falhas de entrega de medicacao de sete pacientes e ainda salvar a vida de dois pacientes que precisavam de medicacao de urgencia, sendo um com risco iminente de morte.

As Leucemias agudas de linhagem ambigua sao leucemias que nao mostram clara evidencia de diferenciacao ao longo de uma unica linhagem e correspondem a menos de 4% de todas as leucemias agudas. Incluem as leucemias agudas indiferenciadas, aquelas que nao apresentam antigenos de nenhuma linhagem especifica, e leucemias agudas de fenotipo misto, aquelas que apresentam blastos que expressam antigenos de mais de uma linhagem (bifenotipicas) ou ainda dois tipos de blastos em um mesmo paciente (biclonais). E importante ressaltar que na literatura as leucemias agudas de linhagem ambigua apresentam desfechos piores quando comparados a leucemias linfoblastica ou mieloide agudas. Relato de caso Paciente do sexo feminino, 62 anos, previamente hipertensa e dislipidemica refere evolucao de 3 meses com inapetencia, sonolencia, astenia intensa e dificuldade para realizar pequenas atividades diarias, alem de febre nao aferida. Nega sangramentos. Ao exame apresentava palidez cutânea, sem linfonodomegalias ou visceromegalias. Hemograma mostrou anemia (Hemoglobina: 8.7g/dL), leucocitose 29590 leucocitos/dL com 67% de blastos e plaquetopenia (54.000/Ul). Na analise de sangue periferico morfologicamente foram identificados dois tipos de blastos, um de tamanho pequeno e com formato regular e cromatina lisa, e outro com tamanho mediano, citoplasma mais abundante e granular. A analise imunofenotipica caracterizou a presenca de duas populacoes de blastos CD34 positivos, uma delas de linhagem linfoide B imatura, com CD19, CD79a e CD10 positivos (58.9% dos blastos) e a segunda populacao de linhagem mieloide com MPO positivo fraco, CD13/CD33 e CD117 positivos (34.2% dos blastos). Os blastos mieloides apresentavam ainda expressao anomala de marcador CD56. A citogenetica evidenciou apenas oito metateses, seis delas com suspeita de alteracoes no cromossomo 7 e 11. A analise por FISH demonstrou a presenca de um sinal extra do gene KMT2A (MLL), da regiao 11q23, e perda do cromossomo 7q31 em 80% das celulas analisadas. Pesquisa molecular de BCR-ABL foi negativa. Assim, apos a confirmacao do diagnostico de Leucemia Aguda Biclonal (mieloide e linfoide B) com alteracao no gene 11q23 e perda do cromossomo 7, foi iniciado tratamento com protocolo Hyper-CVAD. Como intercorrencia a paciente evoluiu com ulceras orais, neutropenia febril e uma trombose venosa profunda em membro inferior direito, com necessidade de anticoagulacao por todo o tratamento e transfusoes mais permissivas de plaquetas. A avaliacao da medula ossea apos o primeiro ciclo de quimioterapia apresentou remissao completa morfologica e presenca na imunofenotipagem de 1.5% de blastos da linhagem linfoides B imatura e 3.9% de blastos da linhagem mieloide, ambos com fenotipo semelhante ao encontrado no diagnostico (Leucemia biclonal B/mieloide).

Paciente feminina, 39 anos, assistente social, com histórico de implante de CDI aos 15 anos por diagnóstico de Cardiomiopatia hipertrófica. Encaminhada pela equipe da Reumatologia em agosto de 2020 com longo histórico hospitalar prévio. Há 2 anos iniciou quadro de dor intermitente em região torácica, associado a sintomas de dispneia aos grandes esforços e episódios eventuais de hemoptise leve. Radiografia de Tórax mostrava múltiplas opacidades nodulares pulmonares bilaterais, imagens estas melhor caracterizadas em Tomografia de Tórax de 25/10/18: vistos múltiplas nodulações, a maioria de localização subpleural, as maiores no lobo médio (41 mm) e língula (48 mm), com densidade de partes moles e calcificações grosseiras inclusas, além de cistos de paredes finas no lobo inferior esquerdo e lesão escavada com componentes sólidos em lobo médio. Na ocasião foi realizado um lavado broncoalveolar, livre de alteração histopatológica significativa, em material paucicelular. Após quase um ano de seguimento com pneumologista externo foi realizado biópsia pleural por videotoracoscopia, a amostra resultou em infiltrado inflamatório crônico inespecífico, sendo seguido o acompanhamento ambulatorial. Estudos complementares foram realizados para etiologia neoplásica, infecciosa ou mesmo vasculite associada a ANCA, todas condições descartadas. Paciente então evoluiu com derrame pleural bilateral, volumoso a esquerda, sendo necessário internação hospitalar e então submetida a drenagem torácica, cuja citologia oncótica resultou negativa e nova investigação com exames evidenciou positividade de anticorpos antinucleares 1:640 com padrão nuclear pontilhado grosso, anti-Ro/SSA e anti-La/SSB positivos. Com a hipótese de Síndrome de Sjögren (SS) foi iniciado tratamento com Prednisona, recebendo alta e ainda posteriormente, fez-se uso de Micofenolato Mofetil por 7 meses. Uma vez em nosso serviço em 2020, após revisão do caso, foi optado pela realização de nova biópsia pulmonar percutânea guiada por tomografia. Resultado da Anatomia Patológica: Parede de via aérea com inflamação crônica com componente de células gigantes tipo corpo estranho e fibrose associada à presença de material amorfo, focalmente ossificado, compatível com amiloide, com positividade a Vermelho do Congo. Feito então eletroforese de proteínas e imunoeletroforese sérica e urinária, sem apresentar evidência de componente monoclonal, dosagem de cadeias leves livres kappa/lamba normal e análise de medula óssea normocelular, com ausência de plasmócitos clonais. Diante dos achados ficou confirmado o diagnóstico de Amiloidose Pulmonar. A paciente segue bem clinicamente, respirando em ar ambiente e com boa saturação de oxigênio, sem uso de terapia imunossupressora. Relevância clínica: Apresentamos um caso de Amiloidose pulmonar tipo predominantemente nodular em paciente do sexo feminino com SS, doença auto-imune linfoproliferativa de apresentação variável, que pode raramente levar a Amiloidose de cadeia leve (AL) órgão específica, na ausência de acometimento sistêmico. As características clinicas e radiológicas de tal entidade são escassas; mulheres representam mais de 90% dos casos e a maioria delas parece ser sintomática. Os nódulos e/ou formas císticas pulmonares, com calcificação e cavitação, são achados frequentes na imagem torácica. Não há dados que suportem uma intervenção terapêutica categórica e a observação clínica pode ser suficiente.

A APCV e uma doenca rara que envolve a reducao acentuada dos precursores eritroides na medula ossea (MO) e anemia severa. Quando associada a discrasias de celulas plasmaticas, o tratamento da inibicao dos eritrocitos mediada por paraproteinas pode levar a resolucao da doenca. Aqui, relatamos um caso de um homem de 50 anos, que consultou seu medico com queixa de astenia, dor em membros inferiores com 3 anos de evolucao que estava investigando quadro de anemia refrataria a tratamento com sulfato ferroso. Hemoglobina basal na ocasiao era 6,2 g/dL. Em investigacao em servico externo, mielograma demonstrou MO com celularidade diminuida, raros precursores eritroides, com displasia de todas as series e foi aventada hipotese de Sindrome Mielodisplasica. Durante 2 anos permaneceu apenas com suporte transfusional de hemacias quinzenal e fez uso de eritropoetina 3 vezes por semana durante 8 meses sem sucesso. Paciente foi entao, encaminhado ao servico de Transplante de Medula Ossea (TMO) do Hospital de Clinicas (HC-UFPR) para avaliacao. Exames na investigacao inicial do servico demonstraram anemia normocitica normocromica severa. Analise de MO demonstrou hipercelularidade com retardo maturativo eritroide e dismegacariopoiese, sendo contra indicado TMO. Paciente foi devolvido ao servico de origem, onde fez tratamento com 8 ciclos de Azacitidina, sendo o mesmo suspenso por baixa tolerância e ausencia de resposta satisfatoria e mantendo necessidade de transfusoes quinzenais. Foi, entao, reencaminhado para o HC-UFPR para nova avaliacao. Nunca foi necessaria transfusao de plaquetas e paciente nunca apresentou quadro de infeccao. Nova analise de MO mostrou material hipocelular, linhagem eritroide intensamente diminuida com retardo maturativo. Tambem foram identificadas 4% celulas plasmaticas no mielograma e imunofenotipagem, essas com fenotipo anormal, clonal, sugerindo MGUS. Na analise imunohistoquimica observou-se retardo maturativo, desorganizacao eritroide e dismegacariopoiese. Cariotipo 46 XY(20). Solicitado entao eletroforese de proteinas (EP) que foi positiva para proteinas monoclonais na concentracao de 25,7% e imunofixacao serica (IFS) demonstrou presenca de 2 componentes monoclonais: Igg/LAMBDA. Paciente iniciou, entao, tratamento com Bortezomibe 1,3 mg/m3 semanal. A APCV relacionada a MGUS nao e comum, com poucos relatos na literatura. No entanto, estudos populacionais mostram que cerca de 3% da populacao geral com 50 anos ou mais tem MGUS. O mecanismo e incerto, mas acredita-se que proteinas monoclonais causam inibicao da producao e maturacao de eritrocitos mediadas por paraproteinas. Portanto, em casos de APCV onde causas ou associacoes mais comuns foram descartados, propomos que EP, IFS e a analise de cadeias leves livres sejam realizados como parte da investigacao. Isso e importante porque o tratamento da paraproteinemia relacionada a discrasia de celulas plasmaticas pode levar a resolucao doenca, proporcionando independencia transfusional e, consequentemente, qualidade de vida ao paciente.

Introdução: As neoplasias mielodisplásicas/mieloproliferativas (SMD/NMP) são neoplasias mieloides clonais com achados clínicos, laboratoriais ou morfológicos que direcionam para o diagnóstico de síndrome mielodisplásica e outros mais sugestivos de neoplasias mieloproliferativas. Relato do caso: W.A.R., sexo masculino, 56 anos, aposentado, ex-etilista (20 aos 35 anos), portador de insuficiência venosa com úlcera varicosa em membro inferior esquerdo, sem outras comorbidades. Há 5 anos com história de anemia, tratado com modificações na dieta, sem continuidade do seguimento. Em abril de 2021 iniciou quadro hematúria, gengivorragia e hematomas em membros inferiores. Buscou atendimento na cidade de origem sendo detectado anemia e plaquetopenia. Foi internado por 4 dias, recebeu transfusão de 3 concentrados de hemácias e 8UI de plaquetas e alta com os seguintes parâmetros hematimétricos (Hb 8,5 g/dL, leucócitos de 8700 x 109/L e plaquetas de 13.000 x 109/L). Após uma semana, procurou novamente atendimento recidiva dos sintomas, exames evidenciaram Hb 4,3 g/dL, VCM 85 fL, Leucócitos de 8600 x 109/L com diferencial normal e Plaquetas 5.000 x 109/L. Recebeu suporte transfusional e alta hospitalar. Evoluiu com dor intensa em abdome superior e flanco esquerdo. Exames desta ocasião revelavam anemia (Hb 10 g/dL), leucócitos de 59.130 x 109/L com 6% de blastos e plaquetas de 16.000 x 109/L, motivo pelo qual foi transferido ao HCPR. Ao exame físico da admissão, apresentava-se em regular estado geral, emagrecido, hipocorado, com dor à palpação abdominal, sem visceromegalias ou linfonodomegalias. Os exames laboratoriais revelavam (realizados 25 dias após os primeiros exames) Hb 9,8 g/dL, VCM 85,2, Leucócitos 57.620 x 109/L, Plaquetas 19.000 x 109/L, desidrogenase lática 1224 mg/dL, ácido úrico 5,9 mg/dL. A avaliação de medula óssea foi realizada, sendo que o mielograma (Fig.1). evidenciou uma medula hipercelular, maturação anormal na linhagem eritroide, células da linhagem granulocítica degranuladas e megacariócitos pequenos e com núcleos hipolobulados, 5% de blastos, sem sideroblastos em anel. A imunofenotipagem identificou hiperleucocitose com 6,25% de blastos mieloides e padrão intensamente alterado na maturação neutrofílica, monocítica e eritróide. A pesquisa de JAK2 e BCR-ABL1 foram negativas. O cariótipo convencional foi classificado como complexo (Fig.2), 42̃50, XY, -5[16], +8[14],-11[17],del(13)(q13)[11], del(13)(q13)x2[4],+mar1[10], +mar2[4], +mar3[8], +mar4[2] [cp23]. O paciente recebeu então o diagnóstico de Síndrome Mielodisplásica/Mieloproliferativa pela classificação da Organização Mundial da Saúde de 2017, de elevado risco citogenético. Pela rápida progressão da leucocitose, optou-se por iniciar tratamento com citarabina em baixa dose, e por manter leucocitose após 3 dias de uso foi optado pela associação com hidroxiureia 500 mg 12/12h. Paciente foi encaminhado para transplante de medula óssea alogênico e recebeu solicitação de azacitidina, porém sofreu trauma cranioencefálico e faleceu por hemorragia intraparenquimatosa, no dia 5° de tratamento. Na data do óbito, o paciente apresentava 25.210 x 109/L leucócitos em sangue periférico. Conclusão: As neoplasias mieloproliferativas/mielodisplásicas são desordens raras, em geral com comportamento indolente, com poucas informações robustas acerca da melhor abordagem terapêutica. Infelizmente o paciente do caso evoluiu a óbito antes de ser submetido a tratamento com agente hipometilante e/ou transplante de medula óssea.

Introducao A anemia hemolitica autoimune (AHAI) e um disturbio causado por autoanticorpos direcionados contra eritrocitos proprios. O diagnostico e realizado por meio de exames laboratoriais e evidenciais clinicas de hemolise. Entretanto, e uma doenca clinicamente heterogenea em termos clinicos e terapeuticos, o que dificulta o seu tratamento. Relato do caso A.S.A., sexo feminino, 74 anos, com historia de hipertensao arterial sistemica, hipotireoidismo, asma e obesidade, em uso de sinvastatina, levotiroxina, losartana, hidroclortiazida e alenia. Historico de internacao em 2017 por AHAI com uso de corticoterapia e ciclofosfamida. Internou por anemia severa, sintomatica com dispneia progressiva ha cinco meses sem episodios de sangramentos. Exames laboratoriais apontavam concentracao de hemoglobina de 4,1 g/L e reticulocitopenia de 4.400 mm3/L. O exame de Coombs direto apresentou-se positivo, eluato imunoglobulina G foi reagente em todas as celulas e as crioaglutininas foram negativas, classificando como AHAI a quente. Foi iniciado tratamento com prednisona, realizado a transfusao de um concentrado de hemacias e foi coletada medula ossea. O resultado da medula e investigacao com tomografias que nao demonstraram achados que suportavam a ideia de uma AHAI secundaria. Como nao houve melhora com o uso da prednisona, foi iniciada ciclosporina. No retorno ambulatorial um mes apos, paciente manteve a dispneia relatada e os exames demonstraram concentracao de hemoglobina de 4,5 g/L e ciclosporina 383 ng/mL, dentro do alvo terapeutico. Foi iniciado eritopoetina (EPO) devido a falha terapeutica e efeitos colaterais de descompensacao hepatica da terapia imunossupressora. Um mes apos o inicio da terapia com EPO a concentracao de hemoglobina estava em 6.1 g/dL, atingindo 14.5 g/L com tres meses de tratamento. Apos a suspensao da EPO, a concentracao de hemoglobina manteve-se estavel nos ultimos dois meses de avaliacao e a paciente nao apresentou mais sintomas. Discussao A AHAI provoca uma hemolise descompensada causada pelo sistema imunologico agindo contra o proprio organismo. Na maioria dos casos ocorre uma boa resposta reticulocitaria, e a combinacao de hemolise grave com resposta medular pode levar a alta reticulocitose periferica. Os casos de resposta eritroide baixa, como o apresentado, com reticulocitopenia, sao incomuns e a causa ainda e incerta, podendo apresentar casos graves devido a falta de mecanismos compensatorios. Alem disso, a reticulocitopenia pode estar associada a hiperplasia ou hipoplasia da medula ossea, o que pode indicar uma interacao dos autoanticorpos com linhagens medulares. Estudos recentes comprovam o beneficio da administracao da EPO, com aumento da contagem de reticulocitos e concentracoes de hemoglobina. Como existem casos de refratariedadade aos tratamentos de primeira e segunda linha com uso de corticoesteroides e imunossupressores, a eritropoetina se apresenta como uma alternativa terapeutica promissora. O uso da estimulacao eritropoietica promove uma resposta rapida a anemia e e menos toxico que os medicamentos atualmente utilizados. Portanto, o uso desse tratamento como terceira linha foi uma ferramenta importante que mudou o prognostico da paciente apresentada, caracterizando boa resposta terapeutica.

Background It was hypothesized that preparing for a surgical procedure, taking into account individual patient characteristics, may facilitate the procedure and improve surgical quality. The aim of this study was to compare different case-specific, preoperative mental rehearsal methods before minimally invasive rectal cancer surgery. Methods In this RCT, patients were allocated in a 1 : 1 : 1 : 1 ratio to four groups: systematic mental rehearsal (SMR) using MRI scans; SMR and three-dimensional (3D) virtual models; SMR and synthetic 3D printed models; and routine practice (control group). Surgeons operating on all but the control group underwent mental rehearsal with the visual aids, including axial MRI scans of the pelvis, interactive 3D virtual models reconstructed from axial MRIs, and synthetic models, manufactured by 3D printing. Operations were video-recorded and assessed by two experts blinded to allocation using two validated scores, the Competency Assessment Tool (CAT) and Objective Clinical Human Reliability Analysis (OCHRA). The primary outcome of the study was surgical performance, measured by the CAT. Results Forty-nine patients were randomized and allocated to the four groups. There were 12 participants in each of the control, MRI and SMR, and virtual and SMR groups, whereas the SMR using physical models and simulation group included 13. No difference was observed between groups in median CAT scores (control 30.50, MRI 34.25, virtual 31.75, physical 34.00; P = 0.748, partial η2 0.200, pη2 =0.052–0.088). Time spent not performing dissection was significantly shorter for the SMR with MRI group than for the control (57.5 versus 42 respectively; P < 0.001, pη2 =0.212). Conclusion Mental rehearsal did not affect CAT and OCHRA scores of consultant surgeons. Reference number: ISRCTN 75603704 (https://www.isrctn.com).

This dataset is composed of correlated audio recordings and labels of ingestive jaw movements performed during grazing by dairy cattle. Using a wireless microphone, we recorded sounds of three Holstein dairy cows grazing short and tall alfalfa and short and tall fescue. Two experts in grazing behavior identified and labeled the start, end, and type of each jaw movement: bite, chew, and chew-bite (compound movement). For each segment of raw audio corresponding to a jaw movement we computed four well-known features: amplitude, duration, zero crossings, and envelope symmetry. These features are in the dataset and can be used as inputs to build automated methods for classification of ingestive jaw movements. Cow´s grazing behavior can be monitored and characterized by identifying and analyzing these masticatory events. Fil: Vanrell, Sebastián Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina Fil: Chelotti, Jose Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina Fil: Bugnon, Leandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina Fil: Rufiner, Hugo Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina Fil: Milone, Diego Humberto. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; Argentina Fil: Lacambra, Emilio. California Davis; Fil: Galli, Julio Ricardo. Facultad de Ciencias Agrarias; Argentina

Introduction Stiff person syndrome (SPS) is a neurological disorder characterized by muscle rigidity primarily in the truncal muscles, commonly associated with autoantibodies to the glutamic acid-decarboxylase 65 kD receptor (GAD65). There is limited epidemiological information on patients with SPS. Methods We performed a retrospective case review using the National United States Veterans Affairs Health Administration electronic medical record system. We analyzed prevalence, demographics, disease characteristics, and treatment outcomes in SPS patients who were anti-GAD65 antibody positive. Results Fifteen patients met our criteria. Point prevalence was 2.06 per million, and period prevalence was 2.71 per million. Men to women ratio was 14:1. All patients benefitted from treatment with symptomatic antispasmodic agents. Ten of 15 patients received intravenous immunoglobulin, with a majority demonstrating stable or improved modified Rankin scores. Discussion This investigation was a large North American epidemiological study of SPS with predominantly male patients. Symptomatic therapy was beneficial for most patients, with less clear sustained benefit of immunotherapy. Muscle Nerve 58:801-804, 2018.

Introducao A leucemia promielocitica aguda (LPA) e uma forma rara de leucemia mieloide aguda, associada a uma alta incidencia de morte precoce devido a ocorrencia frequente de uma diatese hemorragica abrupta, porem que tornou-se uma doenca altamente curavel com o tratamento contemporâneo, que consiste em acido trans-retinoico (ATRA) e quimioterapia a base de antraciclina. Relato do caso Paciente do sexo masculino, 56 anos, com historia de Leucemia Promielocitica Aguda, com diagnostico em dezembro de 1999, submetido a tratamento de inducao com ATRA, seguida por 2 ciclos de consolidacao esquema DOM (Doxorrubicina, Vincristina e Mitoxantrona) e manutencao com ciclos quinzenais de ATRA por 1 ano. Entrou em remissao apos a consolidacao, recebeu alta do acompanhamento ambulatorial no ano de 2010. Portador tambem de doenca ulcerosa peptica em uso de pantoprazol 40 mg/dia. Em agosto de 2020 iniciou quadro de dor em hipogastrio, motivo que o levou a procurar atendimento com medico urologista. Apresentava tambem queixa de dores osseas em gradil costal e sangramento facil ao se barbear. Durante a investigacao com exames laboratoriais observou-se a presenca de anemia, plaquetopenia e blastos granulares no sangue periferico. Admitido no HCPR em bom estado geral, hidratado, hipocorado 1+/4+, anicterico, sem alteracoes no exame fisico segmentar. Os exames laboratoriais da admissao apresentavam Hb 11,5 g/dL, Ht 34%, Leucocitos 7330 x 109/L, Neutrofilos de 147, 92% de promielocitos anormais, Plaquetas 68.000 x 109/L, Tempo de protrombina - Relacao normatizada internacional (RNI) 1,53, Tempo de tromboplastina parcial ativada - relacao 1,11, Fibrinogenio 115 mg/dL, Desidrogenase latica 256 U/L, Creatinina 1,11 mg/dL. Submetido a avaliacao de medula ossea com mielograma com medula ossea hipercelular apresentando predominio de mais de 90% de blastos de tamanho mediano a grande, de formato irregular, nucleos irregulares sendo alguns em halteres, citoplasma abundante intensamente granular, com presenca de bastonetes de Auer e Faggot cells (Fig.1). A imunofenotipagem documentou 84,2% de blastos com fenotipo sugestivo de leucemia promielocitica aguda. O cariotipo convencional teve como resultado 46, XY, sendo que quatro metafases apresentaram material adicional no braco longo do cromossomo 15, provavel que seja um derivativo da translocacao (15;17). A avaliacao por FISH confirmou a translocacao (15;17) (Fig 2.). Por apresentar hipocinesia difusa no ecocardiograma transtoracico, com fracao de ejecao do ventriculo esquerdo de 45%, alem de dose cumulativa de antraciclicos elevada (>700 mg/m2), foi optado por iniciar tratamento com trioxido de arsenio (ATO) 0,15 mg/kg/dia e acido trans-retinoico (ATRA) 45 mg/m2/dia. Durante a inducao, houve necessidade de suspensao do ATRA por 2 dias por sindrome retinoide, com reducao de 50% da dose na reintroducao e suspensao do ATO em 2 ocasioes por aumento do intervalo QTc. Observou-se remissao morfologica apos inducao. Submetido posteriormente a quatro ciclos de consolidacao em regime ambulatorial com ATRA + ATO, sem intercorrencias. Pesquisa de PML-RARα indetectavel ao termino do tratamento. Conclusao Os casos de recaida de LPA correspondem a 10 a 15% segundo dados de literatura, sendo que a maioria acontece nos primeiros anos de seguimento apos o tratamento. O tratamento utilizando ATO em associacao com ATRA e uma excelente opcao terapeutica de resgate para esses pacientes.

Paciente feminina, 68 anos, aposentada. Encaminhada da UBS em fevereiro de 2020 devido ao achado de múltiplos nódulos pulmonares sólidos esparsos bilaterais, não calcificados, de contornos irregulares e espiculados medindo até 1,9 cm, durante investigação de quadro de perda ponderal há 1 ano. Histórico de internamento em novembro de 2019 em serviço externo para realização de biopsia pulmonar, quando apresentou pneumotórax após procedimento com necessidade de drenagem torácica e hemorragia digestiva alta por úlcera duodenal, controlada por hemostasia endoscópica e suporte transfusional. Portadora de HAS, Hipotireoidismo e relato de quadro de dor articular difusa de longa data há 15 anos, porém sem definição diagnóstica de doença reumatológica. Assintomática respiratória. O resultado da biopsia pulmonar à Anatomia Patológica evidenciou tecido pulmonar com Amiloidoma, confirmado pelas colorações especiais Vermelho Congo e Cristal Violeta, sendo descartado infecção granulomatosa ou fúngica associada. Pela Hematologia, em exames de investigação revelou-se presença de elevação de imunoglobulina G – 3.457 e de B2microglobulina – 3.593, pico de base ampla na região das gamaglobulinas (3,16 g/dl) em eletroforese de proteínas sérica, presença de banda monoclonal IgG/lambda à imunoeletroforese e ausência de proteinúria. Em avaliação de medula óssea, 1,3% de células plasmáticas, sendo que 0,2% destas apresentam fenótipo anormal (CD56 forte com CD19 e CD45 negativos), porém policlonais. Ecocardiograma, ventrículo esquerdo pouco hipertrofiado com disfunção diastólica grau I, VHS moderadamente elevado, radiografia de mãos apenas demonstrando desmineralização óssea e redução de espaço articular único. Feito biópsia de gordura abdominal, descartando-se quaisquer alterações histológicas e também não houve achados de focos neoplásicos nos estudos de extensão com tomografias de abdome e pelve. Durante o acompanhamento, ocorreu estabilização espontânea do peso corporal. Relevância clínica: A Amiloidose é um grupo heterogêneo de doenças relacionadas a deposição extracelular de fibrilas compostas por subunidades de baixo peso molecular de uma variedade de proteínas. A primeira descrição de Amiloidose localizada no trato respiratório inferior foi feita pelo alemão Lesser em 1887, podendo a apresentação pulmonar ser traqueobrônquica, nodular parenquimatosa (amiloidoma) ou septal alveolar, com idade média de acometimento de 67 anos. Usualmente no tipo nodular, as lesões possuem contornos lobulados em localizações subpleurais bilaterais de tamanhos diferentes (0,5-15 cm) e crescimento lento sem regressão, sendo frequente um curso assintomático e de bom prognóstico. Em aproximadamente 20% de tais casos uma proteína monoclonal é detectada. Na paciente encontramos lesões nodulares difusas em parênquima pulmonar, juntamente com sintomas sistêmicos, podendo tratar-se de Amiloidose reativa (AA). A diferenciação entre Amiloidose AL devido à discrasia de células plasmáticas, já que há imunoeletroforese com componente monoclonal, poderia ser confirmada com a determinação precisa da proteína amilóide envolvida por espectometria de massa, exame que não é disponível no nosso serviço. O manejo é dependente da gravidade dos sintomas e do tipo da proteína amiloide acometida; na forma primária intervenções são pouco recomendadas enquanto houver ausência de sintomas respiratórios.

Descricao do caso Paciente feminina, 26 anos, caixa de mercado. Encaminhada em setembro de 2020 por hematologista externo para avaliacao de leucocitose e trombocitose progressivas pos-esplenectomia. Historico de diagnostico de Purpura Trombocitopenica Idiopatica (PTI) identificada no segundo mes da gestacao em setembro de 2016, atraves de hemograma de rotina pre-natal, o qual mostrou plaquetopenia (nadir = 1000). Realizado tratamento com corticoterapia, sem apresentar melhora significativa, transfusao de 50 concentrados de plaquetas no total e doses de imunoglobulina intravenosa (IgIV) durante o acompanhamento em outro servico. Optou-se pela extensao do uso da Prednisona 1 mg/kg/dia e desmame lento durante mais de seis meses, confirmando-se a refratariedade as terapias instituidas. Evoluiu com Sindrome de Cushing, diabetes gestacional, doenca hipertensiva especifica da gestacao e obito fetal na trigesima semana. Dois meses apos, em abril de 2017, foi submetida a esplenectomia apos nao apresentar resposta terapeutica com nova dose de IgIV e no 13° dia pos-operatorio evidenciou-se trombose de veia porta, com necessidade de enterectomia do intestino delgado nao viavel (cerca de 1,2 m) e entero-enteroanastomose. Apos o procedimento, passou a apresentar plaquetose significativa, com 677 mil um mes apos o procedimento, chegando a mais de um milhao e meio de plaquetas em setembro de 2020, associado a leucocitose maior que 50 mil. A biopsia de medula ossea (MO) externa de agosto de 2019 mostrou MO normocelular para a idade em fragmento superficial e tangencial, com as tres linhagens presentes e arcabouco reticular preservado, sem sinais de fibrose. Ao fim da primeira avaliacao em nosso servico, foi constatada anemia ferropriva decorrente de hemorragia digestiva alta expressiva no inicio do mes, leucocitose com desvio a esquerda, eosinofilia e basofilia de evolucao progressiva associadas a plaquetose, sendo levantada a hipotese de neoplasia mieloproliferativa. A pesquisa do transcrito BCR-ABL1 resultou positiva, estabelecendo-se entao o diagnostico de leucemia mieloide cronica em outubro de 2020 e iniciado tratamento com Imatinib 400 mg. Na ultima consulta, em 2 de agosto de 2021, apresentava resposta hematologica completa e boa tolerância ao medicamento, com nivel de doenca detectavel molecularmente menor que 10% apos 3 meses de terapia alvo. Discussao A Trombocitopenia imune (PTI) caracteriza-se pela reducao da quantidade de plaquetas presentes na circulacao sanguinea em decorrencia de um mecanismo autoimune. O diagnostico e de exclusao apos todas as causas potenciais deste achado terem sido investigadas e descartadas. Um dos tratamentos de segunda linha e a esplenectomia, sendo que a trombocitose reativa e um evento comum e afeta 75 a 90% dos pacientes pos-esplenectomia, apresentando os maiores valores entre 10 a 20 dias do pos-operatorio e, na maioria dos casos, persistindo por 2 a 3 meses. Em alguns casos persiste indefinidamente, podendo estar associada a eventos tromboticos e hemorragicos. Entretanto, a ocorrencia de trombose de veia porta nestes casos e rara e pode ocorrer ate 3 anos apos o procedimento, sendo uma manifestacao de alarme para prosseguir a investigacao, como no caso relatado. Outra correlacao observada neste caso e o desenvolvimento de LMC precedida pela PTI, a qual e pouco relatada na literatura.

Estimating forage intake and monitoring behavior of grazing livestock are difficult tasks. Real-time detection and classification of events like chew, bite and chew-bite are necessary to estimate that information. It is well-known that acoustic monitoring is one of the best ways to characterize feeding behavior in ruminants. Although several methods have been developed to detect and classify events, their implementation is restricted to desktop computers, fact that confines their application to off-line analysis of a reduced number of animals. In this work, we present the design and implementation of an electronic system specifically developed for real-time monitoring of feeding patterns in dairy cows. The system is based on an embedded circuit to process the sound produced by the animal in order to detect, classify and quantify events of ruminant feeding behavior. The system implements an algorithm recently developed, which was adapted to be executed on a microcontroller-based electronic system. Only the results of sound analysis are stored in flash memory units. In addition to sound information, data from a GPS receiver is also stored, thus building a package of information. A microcontroller with power management technology, combined with a high-efficiency harvesting power supply and power management firmware, enables long operational time (more than five days of continuous operation). The system was evaluated using audio signals derived from the feeding activity of dairy cows that were acquired under normal operational conditions. The system correctly detected 92% of the events (i.e. considering them as possible events without making a classification). When the three types of events (i.e. chew, bite and chew-bite) were considered for classification, the recognition rate was about 78%. These results were obtained using reference labels provided by experts in ruminant ingestive behavior. The technology presented within this publication is protected under the international patent application PCT/IB2015/053721. Fil: Deniz, Nestor Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina Fil: Chelotti, Jose Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina Fil: Galli, Julio Ricardo. Universidad Nacional de Rosario; Argentina Fil: Planisich, Alejandra M.. Universidad Nacional de Rosario; Argentina Fil: Larripa, Marcelo J.. Universidad Nacional de Rosario; Argentina Fil: Rufiner, Hugo Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina. Universidad Nacional de Entre Ríos; Argentina Fil: Giovanini, Leonardo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina

Background:Low-intensity pulsed electromagnetic fields (PEMF) have been shown to improve gait parameters in frail older adults.1 Furthermore, the continuous exposure to PEMF (up to 1 year) have been demonstrated to produce progressive improvements in self-selected gait speed in older adults at risk of falling.2Objectives:To investigate the effects of two different treatment regimens of PEMF on physical performances in older adults presenting with rheumatoid arthritis (RA), osteoarthritis (OA) or severe osteoporosis (OP).Methods:Older adults presenting with RA, OA or OP, at increased risk of falls, evaluated in our Falls Prevention Clinic, were considered for a prospective observational study investigating the effects of PEMF on physical performances. PEMF were supplied by the THS 280 E device (THS-Therapeutic Solutions Srl, Milan, Italy). It provides a new therapeutic approach, named TEPS (Triple Energy Postural Stabilization), that represents an evolution of physical therapy.1,2 On the basis of the physician judgment, PEMF were administered following an intensive protocol, every 45 days (PEMF-45), or a standard validated protocol1,2, every 60 days (PEMF-60). All subjects were assessed at baseline and every 3 months with the following tests: 4 meters gait speed test [4MGS, seconds (sec)], timed up and go test (TUG, sec), chair stand test (CST, sec), short physical performance battery (SPPB, score), and hand grip strength (HGS) by hand dynamometer (Kg). Demographic, anthropometric and clinical characteristics, including pharmacological treatments and functional status were evaluated at baseline. Clinical and adverse events were assessed every 45 or 60 days after PEMF administration.Results:Overall, 94 patients were enrolled between January and December 2020. Of these, 43 subjects (N=33 PEMF-45, N=11 PEMF-60) with a valid 6-month follow-up assessment were considered for the current analysis. The two groups were comparable regarding the main baseline characteristics, and similar % of patients presented with RA, OA or OP. Mean age (±SE) was 78±7 in PEMF-45 and 77±7 in PEMF-60. As expected, all physical performance tests improved significantly from baseline to 6 months in both groups. Mean (±SE) 4MGS increased significantly more in PEMF-45 (from 3.24±0.12 sec to 2.83±0.18 sec) compared to PEMF-60 (from 3.22±0.21 sec to 3.02±0.30 sec, p=.018). Likewise, mean (±SE) CST improved more in PEMF-45 (from 12.4±0.9 sec to 8.7±0.4 sec) compared to PEMF-60 (from 11.1±1.5 sec to 9.8±0.7 sec, p=.002). No significant difference between groups was found for the other tests, although a trend toward better results in PEMF-45 was manifest: SPPB improved by 6.4% in PEMF-45 and by 3.0% in PEMF-60, and TUG decreased by 7.8% in PEMF-45 and by 6.1% in PEMF-60. During the 6 months observation period no adverse event was observed.Conclusion:Preliminary results of our ongoing prospective observational study suggest that a more frequent administration of PEMF produces greater improvements in some but not all physical performance parameters compared to a standard validated regimen1,2.References:[1]Giusti A et al., Geriatr Gerontol Int 2013. 2Giusti A et al., J Am Geriatr Soc 2014.Disclosure of Interests:Massimo Giovale: None declared, Giuseppina Tramontano: None declared, Rossana Galli: None declared, Simone Rando: None declared, Andrea Giusti Speakers bureau: UCB, Amgen, Kyowa Kirin, Abiogen Pharma, and Eli Lilly, outside the submitted work, Consultant of: EffRx and Abiogen Pharma, outside the submitted work, Lorenzo Bandi: None declared, Francesca Russo: None declared, Stefano Rampoldi Employee of: THS Therapeutic Solutions SRL, Luigi Carlo Bottaro: None declared, Gerolamo Bianchi Speakers bureau: Abbvie, Abiogen Pharma, Amgen, BMS, Celgene, Eli Lilly, GSK, Janssen-Cilag, Medac, MSD, Novartis, Pfizer, Roche, Sanofi, Genzyme and Servier, outside the submitted work

Assessment of both grazing behavior and herbage intake are two very difficult tasks that can be concurrently accomplished by means of accurate detection, classification and measurement of grazing events such as chews, bites and chew-bites. It is well known that acoustic monitoring is among the best methods to automatically quantify and classify ingestive and rumination events in grazing animals. However, most existing methods of signal analysis appear to be computationally complex and costly, and are therefore difficult to implement. In this work, we present and test a novel analysis system called Chew-Bite Real-Time Algorithm (CBRTA) that works fully automatically in real-time to detect and classify ingestive events of grazing cattle. The system employs a directional wide-frequency microphone facing inwards on the forehead of animals, and a coupled signal analysis and decision logic algorithm that measures shape, amplitude, duration and energy of sound signals to iteratively detect and classify ingestive events. Performance and validation of the CBRTA was determined using two databases of grazing signals. Signals were recorded on dairy cows offered either, natural pasture (N=25), or experimental micro-swards in indoor controlled environment (N=50). The CBRTA exhibited a simple linear complexity capable to execute 50 times faster than real-time and without undermining overall recognition rate and accuracy when signals were processed at 4 kHz sampling frequency and 8 bits quantization. Furthermore, CBRTA was capable to detect ingestive events with a 97.4% success rate, while achieving up to 84.0% success for their classification as exclusive chews, bites or composite chew-bites. The methodology proposed with CBRTA has promising application in embedded microcomputer systems that necessarily depend on fast real-time execution to minimize computational load, power source and storage memory. Such a system can readily facilitate the transmission of processed data through wireless network or the storage in an onboard device. Fil: Chelotti, Jose Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina Fil: Vanrell, Sebastián Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina Fil: Milone, Diego Humberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina Fil: Utsumi, Santiago A.. Michigan State University; Estados Unidos Fil: Galli, Julio Ricardo. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias; Argentina Fil: Rufiner, Hugo Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; Argentina Fil: Giovanini, Leonardo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Instituto de Investigación en Señales, Sistemas e Inteligencia Computacional; Argentina

Background:Fibromyalgia is a clinical condition characterized by diffuse chronic muscle-skeletal pain, fatigue, sleep/mood disorders and muscular stiffness. The pathogenesis of fibromyalgia remains poorly understood but numerous lines of evidence suggest a role for alterations of both the central and peripheral nervous systems leading to heightened pain sensitivity along with acorollariumof other symptoms1. Low-energy pulsed electromagnetic field (PEMF) has promising data in the prevention of falls in senior individuals and is believed to promote osteogenesis and angiogenesis thus proving promising to treat bone diseases with chronic pain2. No data is available in fibromyalgia.Objectives:To investigate the efficacy and safety of PEMF on fibromyalgia symptoms in a randomized single-blind pilot study.Methods:We enrolled 21 women (median age 59 years, IQR 16,5) affected by fibromyalgia according to the 2010 ACR classification criteria3not receiving chronic medical treatment for pain; patients were randomly allocated to receive PEMF TEPT (triple energy pain treatment) / New Sunrise 280 (THS - Therapeutic Solutions, Milan, Italy) on the selected points (10 agopuncture points) or scrambled points for 20 minutes at baseline (T0) and after 4 (T4) and 8 (T8) weeks. Outcome measures were recorded at T0, T4 and T8 and included FIQ (fibromyalgia impact questionnaire), WIP (widespread pain index), VAS pain, SS (symptom severity scale), and SF-36 (short form 36 health survey questionnaire).Results:Patients receiving the active treatment had a deep reduction of WIP from T0 to T8 (-76% vs -13% in placebo) with a statistically significant difference compared to the placebo group (p=0.0025) (Figure 1). In all endpoints, we observed a general reduction at T4 and T8 compared to T0 also for FIQ, VAS pain, SS, SF-36, regardless of the treatment arm and the decrease was higher in the active treatment arm compared to the placebo group, albeit not reaching statistical significance (Figure 2).Conclusion:The results of our pilot study show that PEMF is more effective than placebo in reducing widespread pain in fibromyalgia while confirming that a placebo effect is clear in this complex disease.References:[1]Targeting network hubs with noninvasive brain stimulation in patients with fibromyalgia Chelsea M. Kaplan, R.E. Harris, UnCheol Lee, Alexander F. DaSilva, George A. Mashour, Steven E. Harte. PAIN: January 2020 - Volume 161 - Issue 1 - p 43-46[2]Yuan J, Xin F, Jiang W. Underlying Signaling Pathways and Therapeutic Applications of Pulsed Electromagnetic Fields in Bone Repair.Cell Physiol Biochem. 2018;46(4):1581-1594[3]Wolfe F, Clauw DJ, Fitzcharles MA, et al. The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res (Hoboken).2010;62:600-61Disclosure of Interests:Massimo Giovale: None declared, Lucia Novelli: None declared, Stefano Rampoldi: None declared, Rossana Galli: None declared, Patrizia Monteforte: None declared, Marica Doveri: None declared, Gerolamo Bianchi Grant/research support from: Celgene, Consultant of: Amgen, Janssen, Merck Sharp & Dohme, Novartis, UCB, Speakers bureau: Abbvie, Abiogen, Alfa-Sigma, Amgen, BMS, Celgene, Chiesi, Eli Lilly, GSK, Janssen, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Sanofi Genzyme, Servier, UCB, Luigi Carlo Bottaro: None declared, Carlo Selmi Grant/research support from: AbbVie, Janssen, MSD, Novartis, Pfizer, Celgene, and Leo Pharma, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and Sanofi-Regeneron, Speakers bureau: AbbVie, Aesku, Alfa-Wassermann, Bristol-Myers Squibb, Biogen, Celgene, Eli-Lilly, Grifols, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi-Genzyme, UCB Pharma

Paraneoplastic neurological syndromes are nonmetastatic complications of malignancy secondary to immune-mediated neuronal dysfunction or death. Pathogenesis may occur from cell surface binding of antineuronal antibodies leading to dysfunction of the target protein, or from antibodies binding against intracellular antigens which ultimately leads to cell death. There are several classical neurological paraneoplastic phenotypes including subacute cerebellar degeneration, limbic encephalitis, encephalomyelitis, and dorsal sensory neuropathy. The patient’s clinical presentations may be suggestive to the treating clinician as to the specific underlying paraneoplastic antibody. Specific antibodies often correlate with the specific underlying tumor type, and malignancy screening is essential in all patients with paraneoplastic neurological disease. Prompt initiation of immunotherapy is essential in the treatment of patients with paraneoplastic neurological disease, often more effective in cell surface antibodies in comparison to intracellular antibodies, as is removal of the underlying tumor.

BACKGROUND: The role of laparoscopy in the setting of perforated appendicitis remains controversial. A retrospective study was conducted to evaluate the early postoperative outcomes of laparoscopic appendectomy (LA) compared to open appendectomy (OA) in patients with perforated appendicitis. METHODS: A total of 1,032 patients required an appendectomy between January 2005 and December 2009. Among these patients, 169 presented with perforated appendicitis. Operation times, length of hospital stay, overall complication rates within 30 days, and surgical site infection (SSI) rates were analyzed. RESULTS: Out of the 169 evaluated patients, 106 required LA and 63 OA. Although operation times were similar in both groups (92 ± 31 min for LA vs. 98 ± 45 for OA, p = 0.338), length of hospital stay was shorter in the LA group (6.9 ± 3.8 days vs. 11.5 ± 9.2, p < 0.001). Overall complication rates were significantly lower in the LA group (32.1 vs. 52.4 %, p < 0.001), as were incisional SSI (1.9 vs. 22.2 %, p < 0.001). Organ/space SSI rates were similar in both groups (23.6 % after LA vs. 20.6 % after OA, p = 0.657). CONCLUSIONS: For perforated appendicitis, LA results in a significantly shorter hospital stay, fewer overall postoperative complications, and fewer wound infections compared to OA. Organ/space SSI rates were similar for both procedures. LA provides a safe option for treating patients with perforated appendicitis.

Mini and Micro percutaneous nephrolithotomy (PCNL) techniques were born with the aim of reducing the trauma associated with the procedure. The main advantages of instrument miniaturization are less bleeding, and more likelihood of a tubeless intervention, with reduced post-operative pain, without interfering with the stone-free rates. The purpose of this chapter is to give practical tips that may be useful to make the procedure safer and prevent complications.

For patients with epilepsy coping with the reaction of other people can sometimes be the most difficult part of living with the disease. In many Countries social implications of epilepsy have determined the institution of legislative interventions to patient’s rights. Therefore the clinician’s responsibility includes helping patients in knowing their rights and the most important laws that have special relevance for people with epilepsy. This article discusses legislative aspects, referring to the Italian law, concerning epilepsy management. Many areas of the life of a person with epilepsy are considered, such as driving, employment, and recreational pursuits.

In this work we propose a novel method to analyze and recognize automatically sound signals of chewing and biting. For the automatic segmentation and classification of acoustical ingestive behaviour of sheep the method use an appropriate acoustic representation and statistical modelling based on hidden Markov models. We analyzed 1813 seconds of chewing data from four sheep eating two different forages typically found in grazing production systems, orchardgrass and alfalfa, each at two sward heights. Because identification of species consumed when in mixed swards is a key issue in grazing science, we tested the possibility to discriminate species and sward height by using the proposed approach. Signals were correctly classified by forage and sward height in 67% of the cases, whereas forage was correctly identified 84% of the time. The results showed an overall performance of 82% for the recognition of chewing events. Fil: Milone, Diego Humberto. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Departamento de Informática. Laboratorio de Investigaciones en Señales e Inteligencia Computacional; Argentina Fil: Rufiner, Hugo Leonardo. Universidad Nacional de Entre Ríos. Facultad de Ingeniería; Argentina Fil: Galli, Julio Ricardo. Universidad Nacional del Litoral. Facultad de Ingeniería y Ciencias Hídricas. Departamento de Informática. Laboratorio de Investigaciones en Señales e Inteligencia Computacional; Argentina Fil: Laca, E.A.. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias; Argentina Fil: Cangiano, Carlos Alberto. University of California; Estados Unidos

Summary: Purpose: Several lines of evidence indicate that there exists a relation between ovarian hormones and epilepsy. Estrogens decrease seizure threshold and increase brain excitability, whereas progesterone has an inhibitory effect and reduces epileptiform activity. Recently considerable interest has turned to neuroactive steroids, a group of progesterone metabolites, as endogenous modulators of excitability of the central nervous system (CNS). Their ability to alter neuronal firing rapidly occurs through interaction with γ-aminobutyric acid (GABA) A receptor complex. In a previous experience, serum allopregnanolone (3α-OH-5α-pregnan-20-one) levels were measured in 15 women with partial epilepsy in the intercritical phase, and no significant differences were found between patients and control subjects. Methods: To find out if there are changes in serum allopregnanolone levels after epileptic seizure, blood samples were drawn immediately, 15 min, and 6 h after a seizure in seven fertile females with partial epilepsy. Results: The most interesting finding is that allopregnanolone increases in serum during the first 15 min after partial seizures (p < 0.05) and decreases after 6 h. Conclusions: These data are consistent with a role for allopregnanolone in the control of neuronal excitability and seizures.

Summary: Purpose: Limited research has focused to date on objective neurophysiological evaluation of daytime sleepiness in patients treated with newer antiepileptic drugs (AEDs), especially when used as monotherapy. This study was aimed at assessing occurrence of daytime sleepiness in newly diagnosed, drug-naive patients with partial epilepsy receiving initial topiramate (TPM) monotherapy. Methods: Daytime vigilance was assessed in 14 consecutive, newly diagnosed and never medicated adult patients with focal epilepsy, receiving monotherapy with TPM. At baseline and 2 months after slowly titrated therapy with TPM, 200 mg/day, patients underwent the Multiple Sleep Latency Test (MSLT), visual simple and choice reaction times (VRT), and self-rated their own degree of sleepiness with the Epworth Sleepiness Scale. A group of 14 age- and gender-matched healthy volunteers served as controls. Results: At baseline, mean daytime sleep latencies on the MSLT were comparable in patients and in controls. Two months after TPM monotherapy, MSLT scores did not significantly change in patients as compared with pretreatment values. Accordingly, subjective daytime sleepiness and VRTs, which were comparable in controls and in untreated patients at baseline, did not change in patients after TPM monotherapy. Conclusions: Study results suggest that an initial short-course monotherapy with TPM, 200 mg/day, does not impair daytime vigilance in newly diagnosed adult patients with partial seizures.

Resumen Se presenta la preparacion de un radiocoloide que permite la marcacion de leucocitos utilizando su capacidad de fagocitosis. Dado que esta funcion es exclusiva de los globulos blancos, no ejerciendola otras celulas sanguineas, se probo la utilizacion de un coloide de fluoruro estannoso marcado con 99m Tc (F 2 Sn- 99m Tc) a fin de marcar dichas celulas en muestras de sangre entera. Mediante tecnicas de separacion celular en gradientes de densidad y adquisicion de imagenes en camara gamma de la distribucion de radioactividad en tubos con Percol 90 %, se observo que la marcacion lograda es selectiva y de alta eficiencia para leucocitos (en todos los casos fue mayor del 70 %), optima reproducibilidad, bajo costo y baja toxicidad celular.

Efficiency of reconstruction algorithms is important to guarantee quality of Nuclear Medicine tomographic images. The algorithms belong to one of two types: analytical or statistical. The Filtered Back Projection (BP) algorithm belongs to the first group and the Ordered Subsets Expectation Maximization (OSEM) algorithm belongs to the second group. The aim of the present paper was to compare both algorithms by means of the Wavelet Transform (WT). This tool was selected because of its capability to divide the image into different frequency levels without losing information about their spatial position. The WT was applied on the Haar basis without decimation in order to compare matrixes of the same size. Attention was drawn to the relative presence of three typical perturbations: Poisson noise, annular artifacts that express a deficient correction to the planar uniformity and attenuation phenomenon. With these purposes, we studied homologue transversal slices of images of homogeneous distribution of activity. The OSEM algorithm not only greatly improves the filtering of the Poisson noise, but also diminishes the annular artifacts, mainly at the image zone that coincides with the rotation center. The intensity of the attenuation phenomenon was the same with both algorithms, except in the peripheral zone where OSEM showed a slightly higher activity than BP. These observations encourage our interest to continue applying the WT not only to identify the artifacts, but also to try to decrease their deleterious influence on Nuclear Medicine images.

Objectives The aim of this study was to assess the concordance on the interpretation of HIV-1 drug-resistance genotypic data by three widely used algorithms: Stanford University Database (SU), TruGene (Visible Genetics, Canada) (VG) and VirtualPhenotype (Virco, Belgium) (VP). Methods Genotypic data from 293 HIV-1-infected individuals with treatment failure was interpreted for 14 antiretroviral drugs by the three algorithms. Results Complete concordant results among the three systems for all the drugs studied were found in 40/293 (13.7%) samples. Low concordance in the interpretation was observed for most nucleoside reverse transcriptase inhibitors (NRTIs), while results agreed highly for all nonnucleoside reverse transcriptase inhibitors (NNRTIs) and most protease inhibitors (PIs). In pair-wise comparisons, discordant interpretations between SU and VP were found in over 50% of the samples for didanosine, zalcitabine, stavudine and abacavir, and the level of disagreement between VG and VP exceeded 40% for the same drugs. Major discrepancies (high-level resistance interpretation by one algorithm with sensitive interpretation by another) were observed between VG and VP in over 10% of the cases for didanosine, zalcitabine, stavudine and abacavir. On the other hand, the three algorithms had concordant results for lamivudine in over 90% of the cases. Conclusions This work demonstrates the great level of discordance in the interpretation of genotyping results among algorithms, clearly showing the necessity for clinical validation. Moreover, these results suggest that a joint effort from the scientific community as well as national and international HIV societies is needed to achieve a consensus for the interpretation of genotypic data.

The aim of the present study was to evaluate the Epi-QoL, a new Italian-specific measure of health-related quality of life (HRQOL) for adults with epilepsy; the clinical variables that affected the HRQOL score were also assessed. The Epi-QoL is a 46-item self-administered questionnaire focusing on six domains: Physical Functioning, Cognitive Functioning, Emotional Well-Being, Social Functioning, Seizure Worry, and Medication Effects. Eight hundred fifteen patients recruited from 24 secondary and tertiary Italian centers for the care of epilepsy were assessed. The results supported the reliability and validity of the Epi-QoL as a measure of HRQOL. The variables that significantly affected HRQOL scores were: geographic area, gender, seizure frequency, prognostic categories, number of medications, comorbidity, presence of cognitive impairment, psychiatric disturbances, and disability. We believe that a new specific questionnaire for the evaluation of HRQOL in Italy can contribute much to the understanding of the influence of epilepsy on patients' lives.

The treatment of progressive myoclonic epilepsy (PME) is largely empirical, even though valproic acid (VPA) is usually considered the drug of first choice. However, VPA should be used with caution in PME due to mitochondrial dysfunction, i.e. in MERRF (myoclonic epilepsy with ragged red fibers) syndrome, because of its interaction with mitochondrial respiration and metabolism. Levetiracetam (LEV) treatment was started in combination with VPA in a patient with typical clinical, histological, and biochemical features of MERRF due to a mutation on the tRNA of Phenilalanine gene. The average myoclonus score improved dramatically, as well as the quality of life and no side effects were observed, even after having withdrawn VPA. LEV may benefit myoclonus in PME of mitochondrial origin without altering mitochondrial function, and it could be considered the drug of first choice for the treatment of myoclonus in MERRF.

Osmotic agents are still the most common treatment for controlling intracranial hypertension (ICH). Mannitol, glycerol, sorbitol, and hypertonic serum saline are the agents currently available. This work was designed to compare mannitol and glycerol in a similar population of brain injured patients, randomly divided into two groups of eight. The following mean day parameters were obtained: number of infusions, hydric balance, mean arterial pressure (MAP), and intracranial pressure (ICP). Cerebral perfusion pressure (CPP) was calculated. Brain computed tomographies (CT) were obtained on arrival, at follow-up whenever justified and at discharge. For comparison of both groups a modified therapeutic intensity level (mTIL) was used. Both agents induced a statistically equally effective decrease on ICP and increase on CPP evaluated at one and two hours post infusion but the mean day mTIL showed a statistically significant difference in favour of glycerol. The possible explanations of this difference are discussed. According to our results mannitol would be most indicated as a bolus to control sudden rises in ICP whereas glycerol would be most indicated as a basal treatment.

gamma-Glutamyltranspeptidase (gamma GT) appears in serum in multiple forms; their significance and clinical utility in hepatobiliary and pancreatic diseases are still a matter of controversy. Electrophoretic separation of the multiple forms of gamma GT on agarose gel was performed in 20 alcoholic patients (six with cirrhosis and 14 with fatty liver) and the results compared with those obtained in 50 healthy volunteers, 43 patients affected with chronic hepatitis C, 36 patients with posthepatitic cirrhosis and in 52 epileptic patients on long-term anti-epileptic medication. Multiple forms of gamma GT were separated into several bands (up to 11), labelled 0a, 0b, 1a, 1b, 2a, 2b, 2c, 3a, 3b, 4a, 4b. In the alcoholic patients nine fractions were detected, and the electrophoretic pattern observed was significantly different from that observed in healthy volunteers and in patients with chronic hepatitis C or posthepatitic cirrhosis. No differences were observed in the electrophoretic patterns in the alcohol abusers and epileptic patients. In alcoholic patients significant differences were observed in the electrophoretic patterns in relation to the degree of liver injury; the electrophoretic patterns in patients with alcohol-related cirrhosis and posthepatitic cirrhosis differed significantly. The separation of multiple forms of gamma GT has high sensitivity and good reproducibility. It may be proposed as a complementary test in the diagnosis of alcoholic liver disease.

mWorld integrates 3D virtual-scene generation tools and synchronous, asynchronous, and time-dependent data communication techniques to enable cooperative 3D design and visualization across networks.

In 40 adult patients with partial epilepsy resistant to carbamazepine (CBZ) monotherapy at the maximum tolerated individual doses, vigabatrin (VGB) was added to reduce seizure frequency further. In an attempt to evaluate potential drug-related visual side effects, visual contrast sensitivity (VCS), i.e., the ability to perceive minimal differences in luminance between adjacent regions of a grating visual pattern, was assessed before and monthly during a 6-month period of VGB add-on therapy and compared with that of a control group of healthy subjects. Twenty-eight patients completed the prescribed 6-month period of trial and were included in the statistical analysis. VCS measured during CBZ treatment showed a clear loss in all explored spatial frequencies. From the second month of VGB treatment on, VCS exhibited a progressive recovery, especially in the medium-frequency range, although only to a partial extent as compared with that in the controls. This effect saturated at the sixth month. Moreover, a different recovery of VCS to vertical and oblique gratings was observed, which likely suggests a drug effect on visual cortex. VGB add-on therapy was both well tolerated and effective in reducing seizure frequency.

The Virtual Studio concept replaces real background sets with computer-generated synthetic scenes. Image sequences combine real foreground action, shot in the studio, with computer generated backgrounds. The Mona Lisa project seeks to develop and integrate technologies (algorithms, software, and hardware) needed to construct, handle, and render 3D models in real time.

Autosomal recessive limb girdle muscular dystrophies (LGMD) type 2A are a group of disorders characterised by progressive involvement of proximal limb girdle muscles and caused by changes in the CAPN3 gene. Involvement of tissues other than the skeletal muscle has not been reported so far. Here we describe the unusual association of LGMD2A and idiopathic generalised epilepsy in a 14-year-old girl.

Objective: To analyze seizure control and treatment in pregnant women with epilepsy. Methods: Seizure control and treatment were recorded prospectively in 1,956 pregnancies of 1,882 women with epilepsy participating in EURAP, an international antiepileptic drugs (AEDs) and pregnancy registry. Results: Of all cases, 58.3% were seizure-free throughout pregnancy. Occurrence of any seizures was associated with localization-related epilepsy (OR: 2.5; 1.7 to 3.9) and polytherapy (OR: 9.0; 5.6 to 14.8) and for tonic-clonic seizures, with oxcarbazepine monotherapy (OR: 5.4; 1.6 to 17.1). Using first trimester as reference, seizure control remained unchanged throughout pregnancy in 63.6%, 92.7% of whom were seizure-free during the entire pregnancy. For those with a change in seizure frequency, 17.3% had an increase and 15.9% a decrease. Seizures occurred during delivery in 60 pregnancies (3.5%), more commonly in women with seizures during pregnancy (OR: 4.8; 2.3 to 10.0). There were 36 cases of status epilepticus (12 convulsive), which resulted in stillbirth in one case but no cases of miscarriage or maternal mortality. AED treatment remained unchanged in 62.7% of the pregnancies. The number or dosage of AEDs were more often increased in pregnancies with seizures (OR: 3.6; 2.8 to 4.7) and with monotherapy with lamotrigine (OR: 3.8; 2.1 to 6.9) or oxcarbazepine (OR: 3.7; 1.1 to 12.9). Conclusions: The majority of patients with epilepsy maintain seizure control during pregnancy. The apparently higher risk of seizures among women treated with oxcarbazepine and the more frequent increases in drug load in the oxcarbazepine and lamotrigine cohorts prompts further studies on relationships with pharmacokinetic changes. Risks associated with status epilepticus appear to be lower than previously reported.

The paper presents a prototype system for cooperative architecture design. The system includes a multi-site cooperative 3D editor and a cooperative and communication support platform. By using the prototype system, the users are able to load a design scene, modify its properties and save the result cooperatively. The online basic cooperative, interactive editing functionality on the designed objects via the communication network has been achieved.

Vagus nerve stimulation (VNS) has been suggested as an adjunctive treatment for drug-resistant epilepsy when surgery is inadvisable. The overall safety profile of VNS seems to be favorable as only minor adverse effects have been described. The purpose of this study was to determine if cardiac vagal tone is eventually modified by short- and long-term VNS. The effects of short- and long-term VNS were evaluated in seven subjects with intractable epilepsy. Autonomic cardiac function has been carried out by means of a 24-h analysis of RR variability at baseline (t(0)), 1 month (t(1), short-term VNS) and 36 months after VNS initiation (t(2), long-term VNS). Frequency- and time-domain parameters were calculated. Periodic cardiological and neurological evaluations were performed.Clinically relevant cardiac effects were not observed throughout the study. Despite the limited number of patients and the variety of data among them, for all the patients, a common trend towards a nocturnal decrease in the high-frequency (HF) component of the spectrum was observed after long-term VNS (mean+/-S.D.: 40+/-18 normalized units (nu) at t(0), 38+/-17 nu at t(1), 18+/-10 nu at t(2); p0.05 of t(2) vs. either t(0) or t(1)). The day-to-night changes in the power of low-frequency (LF) and HF components were significantly blunted after long-term VNS (LF day-to-night change: +16+/-13 nu at t(0) and +15+/-8 nu at t(1) vs. +3+/-13 nu at t(2), p0.02; HF day-to-night change: -18+/-13 nu at t(0) and -13+/-11 nu at t(1) vs. +3+/-12 nu at t(2), p0.003). No significant changes were observed with regard to the time-domain parameters of the heart rate variability. Throughout the neurological follow-up, one subject became seizure-free, three experienced a seizure reduction of50%, two patients of50% and one had no changes in his seizure frequency. Our findings suggest that long-term VNS might slightly affect cardiac autonomic function with a reduction of the HF component of the spectrum during night and a flattening of sympathovagal circadian changes, not inducing, however, clinically relevant cardiac side effects.

This paper presents an original experience in the design of electrical drives. A complete integration has been realised among the design of the motor, power converter and control. This solution became possible thanks to the application of a software tool called Electromechanical System Simulator (EMSS), whose Finite Element Method (FEM) core is Maxwell2D, that allowed the electromagnetic design of the motor and then the generation of a SPICE model of this device so to allow the analysis of the interaction with the power converter and the control structure. This solution presents the interesting aspect of reaching an high detail in the analysis of the electromagnetic field inside the machine without disregarding the circuit-based approach of the converter design.

There is a lot of development currently being carried out on cooperative visualization via communication networks. User interaction is kept to minimum in this kind of development, such as only making marks on the transmitted images, etc. There is relatively less work being done on complicated cooperative interactions, especially real-time cooperative interaction via networks. The work presented in this paper is a challenge to this type of cooperative work. The objective of the system is to allow multiple users to design a 3D scene cooperatively via communication networks in real time. The paper describes the design and communication model of the system, the design and implementation of the protocol to transmit changes in the 3D scene, the database consistency techniques and the implementation of the 3D editor interface. The current implementation status of the system shows that a real-time, full user interaction in 3D cooperative design via communication networks is achievable by our design strategy.

While water, as an industrial commodity, is considered increasingly as a valuable material and the subject of responsible care for the environment, water reuse is increasingly regarded as a tool for substantial reduction in water supply needs, and saving in related costs. A strategic approach to water reuse must be based on a systematic analysis and on the principle that any water user must never use more water of a higher quality than strictly needed. In this paper some hints are given for implementing water reuse in the food processing industry, particularly referring to the practical case of tomato processing for which a case study is also reported. The results clearly show how remarkable environmental and economic advantages can be simply obtained by implementing low investment cost solutions, and that water supply and discharge flow rates can be dramatically reduced without implementing any special water upgrading treatment process. The Journal of Food Technology in Africa Volume 5 Number 1 (January- March 2000), pp. 25-29